The present invention relates to an advantageous process for the preparation of .alpha.-alkoxy-.alpha.-trifluoromethyl-arylacetic esters and -arylacetic acids from arylketo esters. .alpha.-Alkoxy-.alpha.-trifluoromethyl-arylacetic acids, e.g. .alpha.-methoxy-.alpha.-trifluoromethyl-phenylacetic acid, also called Mosher's acid, are important reagents for determining the optical purity of chiral amines (see Synlett 1991, 643).
Process for the preparation of .alpha.-methoxy-.alpha.-trifluoromethyl-phenylacetic acid are known, but all of the known processes are unsatisfactory.
For example, according to J. Org. Chem. 34, 2543 (1969), sodium cyanide is reacted with .alpha.,.alpha.,.alpha.-trifluoroacetophenone in 1,2-dimethoxyethane, then alkylated with dimethyl sulphate, then the nitrile is hydrolysed to give the amide and, finally, the amide is hydrolysed to give the acid. In a variation of this process, instead of the methoxyethane, t-butanol is used and the hydrolyses are carried out using alkaline hydrogen peroxide solution (Tetrahedron 42, 547 (1986)). In both cases, disadvantages are the poor availability of the trifluoroacetophenone, the preparation 20 of which involves the handling of gaseous trifluoroacetyl chloride (boiling point: +2.degree. C.), and the fact that trifluoroacetophenone is only obtainable in moderate yields. In addition, toxic sodium cyanide has to be handled, which signifies extra expenditure, including for disposal. Finally, the hydrolyses produce benzoic acid as secondary component, which because of its ability to sublime, can only be removed with difficulty, as a result of which this method generally only gives products containing benzoic acid.
Another process for the preparation of .alpha.-methoxy-.alpha.-trifluoromethyl-phenylacetic acid (J. Org. Chem. 57, 3731 (1992)) starts from trimethylsilyl trifluoroacetates and .alpha.,.alpha.,.alpha.-trifluoroacetophenone, which are reacted in the presence of the crown ether 18-crown-6. The trichloromethyl group is then hydrolysed using potassium hydroxide/methanol, again producing benzoic acid as secondary component. As well as the disadvantages described above, which are caused by the use of .alpha.,.alpha.,.alpha.-trifluoroacetophenone and the benzoic acid which forms as secondary component, this process also uses an expensive crown ether, which also causes disposal problems.
Finally, Synlett (loc. cit.) describes the reaction of a-keto esters with trifluoromethyl-trimethylsilane and the hydrolysis of the formed trifluoromethyl trimethylsilyl ether with aqueous hydrochloric acid to give the corresponding trifluoromethylhydroxy compound. If benzyl esters are used, then a reaction time of 69 hours is required for formation of the hydroxyl compound (loc. cit., Table 1, line 4), which is almost 3 whole days. In the case of benzoyl formates (=benzoylalkoxy compounds), it is stated that the hydrolysis of the silyl ester presents problems. A useful synthesis of .alpha.-alkoxy-.alpha.-trifluoromethyl-arylacetic acids is thus not practicable in this way.